Biology subjects

Storey, E.

Publications and source records attributed to Storey, E..

4 recordsLinked to original sources

bioRxiv2020

Neuroprotective effects of motherhood on brain function in late-life: a resting state fMRI study.

The maternal brain undergoes structural and functional plasticity during pregnancy and the postpartum period. Little is known about functional plasticity outside caregiving-specific contexts, and whether changes persist across the lifespan. Structural neuroimaging studies suggest that parenthood may confer a protective effect against the ageing process, however it is unknown whether parenthood is associated with functional brain differences in late-life. We examined the relationship between resting state functional connectivity and number of children parented in 220 healthy older females (73.82{+/-}3.53years) and 252 healthy older males (73.95{+/-}3.50years). We compared patterns of resting state functional connectivity with three different models of age-related functional change to assess whether these effects may be functionally neuroprotective for the ageing human parental brain. No relationship between functional connectivity and number of children was obtained for males. For females, we found widespread decreasing functional connectivity with increasing number of children parented, with increased segregation between networks, decreased connectivity between hemispheres, and decreased connectivity between anterior and posterior regions. The patterns of functional connectivity related to the number of children an older woman has parented were in the opposite direction to those usually associated with age-related cognitive decline, suggesting that motherhood may be beneficial for brain function in late-life.

neuroscience↗

bioRxiv2019

Validation of new tools to identify expanded repeats: an intronic pentamer expansion in RFC1 causes CANVAS

Genomic technologies such as Next Generation Sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG)exp] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS families and identified a core ancestral haplotype, estimated to have arisen in Europe over twenty-five thousand years ago. WGS of the four RFC1 negative CANVAS families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders.

genetics↗

bioRxiv2019

Cortical changes associated with parenthood are present in late life

Early parenthood results in changes in cortical thickness in regions related to parental care. However, the enduring effects of this period on the structure of the human brain, and cognition in late-life, is unknown. In an elderly sample, we examined the relationship between the number of children parented (here, 1-6 children) and cortical thickness in 267 males (74.0 {+/-}3.5 years) and 231 females (73.8{+/-}3.5 years). We also compared cognition and cortical thickness between parents of one child and non-parents, in n=36 males (73.4{+/-}3.7 years), and n=46 females (72.8{+/-}3.3 years). We obtained a positive relationship between number of children parented and verbal memory performance, showing increasing memory performance with number of children. For mothers, number of children positively correlated with cortical thickness in the parahippocampal gyrus and negatively correlated with regions of the visual cortex. Mothers of one child showed thinner cortical thickness in the dorsolateral prefrontal cortex and visual cortex compared with childless women. Fathers of one child showed thinner cortical thickness in the anterior cingulate cortex and thicker cortical thickness in the temporal pole compared with childless men. Our results are the first to reveal distributed differences in cortical thickness related to parenthood that are evident beyond the postpartum period. Our findings overlap substantially with the areas found to be altered across pregnancy and the postpartum period, suggesting that neural changes associated with early parenthood persist into older age, and are potentially cognitively beneficial.

neuroscience↗

bioRxiv2018

Longitudinal dentate nuclei iron concentration and atrophy in Friedreich ataxia: IMAGE-FRDA

BackgroundFriedreich ataxia is a recessively inherited, progressive neurological disease characterised by impaired mitochondrial iron metabolism. The dentate nuclei of the cerebellum are characteristic sites of neurodegeneration in the disease, but little is known of the longitudinal progression of pathology in these structures.\n\nMethodsUsing in vivo magnetic resonance imaging, including quantitative susceptibility mapping, we investigated changes in iron concentration and volume in the dentate nuclei in individuals with Friedreich ataxia (n=20) and healthy controls (n=18) over a two-year period.\n\nResultsThe longitudinal rate of iron concentration was significantly elevated bilaterally in participants with Friedreich ataxia relative to healthy controls. Atrophy rates did not differ significantly between groups. Change in iron concentration and atrophy both correlated with baseline disease severity or duration, indicating sensitivity of these measures to disease stage. Moreover, atrophy was maximal in individuals early in the disease course, while the rate of iron concentration increased with disease progression.\n\nConclusionsProgressive dentate nuclei pathology is evident in vivo in Friedreich ataxia, and the rates of change of iron concentration and atrophy in these structures are sensitive to the disease stage. The findings are consistent with an increased rate of iron concentration and atrophy early in the disease, followed by iron accumulation and stable volume in later stages. This pattern suggests that iron dysregulation persists after loss of the vulnerable neurons in the dentate. The significant changes observed over a two-year period highlights the utility of quantitative susceptibility mapping as a longitudinal biomarker and staging tool.

neuroscience↗